Retinoic acids such as 13-cis-retinoic acid and all-trans-retinoic acid are known to have beneficial dermatological effects, i.e. on human skin, and may be applied to retard the effects of photoaging on skin, or to combat acne, or in general to improve skin quality. However, repeated topical application of retinoic acids to human skin for these dermatological purposes may initially cause transient skin irritation (dermatitis) which may be characterized by erythema, scaling, pruritus, and sensations similar to sunburn (1,2). This problem is described in U.S. Pat. No. 4,888,342. Such results are also observed in animals after repeated topical dosing with retinoic acids.
The inflammatory component of retinoic acid induced skin irritation in animals can be demonstrated histologically by an influx of inflammatory cells into the skin. The effect can be quantified biochemically from measurement of increased myeloperoxidase (MPO) activity in skin biopsy punches (3) (MPO is a marker enzyme for neutrophils). In mice, for example, topical retinoic acid induced skin irritation is characterized by an inflammatory response and, after repeated topical applications, epidermal hyperproliferation.
Tocopherols, for example alpha tocopherol (Vitamin E), have long been recognized for their properties as free radical scavenging antioxidants (4). Also, it has been demonstrated that Vitamin E taken orally at a dose of 800 mg can reduce the toxic side effects of 13-cis-retinoic acid (100 mg/m.sup.2) in patients who were treated with this retinoic acid for myelodysplastic syndrome (5).